Biomechanical Aspects of Spinal Cord Injury Thomas R. Oxland PhD PEng Professor & Director...

Biomechanical Aspects of Spinal Cord Injury

Thomas R. Oxland PhD PEngProfessor & Director

Division of Orthopaedic Engineering ResearchDepartments of Orthopaedics & Mechanical Engineering

The University of British Columbia Vancouver Coastal Health Research Institute

UBC – The University of British Columbia

• 40,000 students

• 4,000 faculty

UBC Department of Orthopaedics

• 65 faculty members• 5 teaching hospitals• basic & clinical

research

• seven Divisions– Athletic Injuries– Lower Limb Reconstruction– Upper Limb Reconstruction– Pediatrics– Spine– Trauma– Orthopaedic Engineering

Research

Orthopaedic Engineering Research (DOER)

• the application of engineering principles to clinically relevant problems in the field of Orthopaedics

DOER at UBC

• Thomas Oxland• David Wilson• Heather McKay• Karim Khan• Peter Cripton• Steve Robinovitch• Rizhi Wang• Goran Fernlund• Gail Thornton

• Clive Duncan• Bassam Masri• Don Garbuz• Marcel Dvorak• Brian Kwon • Charles Fisher• Pierre Guy• Peter O’Brien• Robert McCormack• Bill Regan

Research Themes

• Mechanisms of Spine and Spinal Cord Injury [Oxland, Cripton, Kwon, Dvorak,Tetzlaff]

• Etiology of Osteoarthritis [Wilson, MacKay, Cibere]

• Hip Fracture Prevention [McKay, Khan, Robinovitch, Guy]

• Surgical Solutions in presence of Bone Loss– osteoporotic spine [Oxland, Cripton, Dvorak, Fisher]– revision hip [Oxland, Duncan, Masri, Fernlund]

SCI Epidemiology

• ~11,000 new injuries/year in North America (40/million)

• 200,000 chronic injuries• Average age 32 • $9.73 billion/year

– hospitalization, rehabilitation, medication, equipment, loss productivity

-Spinal Cord Injury Information Network - www.spinalcord.uab.edu

ICORD – new home for Spinal Research Centre in Vancouver

•Vancouver General Hospital

•51 principal investigators

•120,000 square feet

•Spinal clinics

•Rehabilitation research

•Molecular Biology

•Bioengineering

•Neuropysiology

February 2008

October 2008

Theme 3-

Develop novel animal models of SCI where damage can be induced within an enclosed vertebral column, thereby more accurately mimicking human SCI.

Can only be achieved through the combined efforts of spine surgeons, biomechanical engineers and neuroscientists working side-by-side.

Theme 3 - Overview

Spinal cord injury represents a

mechanical insult that triggers a

biological response which results in a

wide range of clinical sequelae.

Type of Vertebral Injury

40% Fracture Dislocation

5% Dislocation

Burst Fracture 30%

SCIWORET 10%

SCIWORA 5%

10% Minor Fracture

Sekhon & Fehlings Spine 2001

Spinal Injury

FRACTURE DISLOCATION

BURST FRACTURE

FLEXION-DISTRACTION

Clinical Observation

• the mechanism of column damage correlates with the neurological deficit – Marar 1974, Tator 1983

…. but current treatments do not incorporate injury mechanism!

Methods – Cord/Column

• Surrogate Cord – Silicone gel

– In vivo-like in tension

• Barium Sulfate added

• Oval shaped

Saari MASc 2006

Methods – Specimen Preparation

• Human cervical spines occiput to T2 (n = 6)

• Surrogate head attached to occiput

Saari MASc 2006

Methods – Imaging

• High Speed X-ray

– Industrial X-ray source

• 75kV, 5mA

– 9” image intensifier

– Internal high speed camera

• 1000 frames per second

• 256 x 240 pixels

Image Intensifier

X-ray Source

Saari MASc 2006

Saari MASc 2006

Flexion-compression injury model

Effect of Constraint

Zhu 2008

Compression to the Specimen

Displacement

-25

-20

-15

-10

-5

0

0.5 0.7 0.9 1.1 1.3 1.5

Time (sec)

Dis

pla

cem

ent

(mm

)

35 msec

Zhu 2008

Flexion-Compression (constrained)

Flexion-Compression (unconstrained)

Zhu 2008

Canal Occlusion

130

140

150

160

170

180

190

200

0 10 20 30 40 50 60

compression (mm)

Sp

ina

l c

an

al

are

a (

mm

^2

)

unconstrained

constrained

Zhu 2008

Column-Canal Relationships

constrained unconstrained

Zhu 2008

Pro-Neck-TorTM Standard Helmet

http://injury.mech.ubc.ca http://www.pronecktor.com

Dr. Peter Cripton

15º, Med Stiffness, Extension Escape, Vimpact ~3.2 m/s

Proof of Concept Study – Results:

• Axial Force Escape-Angle Interaction

56% reduction

C4

C5

C6

Greaves 2008

Von Mises StrainCompression

0.320.280.240.200.160.120.080.040.00 0.370.320.280.240.200.160.120.080.040.00 0.370.290.260.220.180.150.110.070.040.00 0.330.290.260.220.180.150.110.070.040.00 0.33

dorsalventralventral

dorsal

Greaves 2008

Von Mises StrainDistraction

0.320.280.240.200.160.120.080.040.00 0.370.320.280.240.200.160.120.080.040.00 0.37

0.110.100.080.070.050.040.030.010.00 0.120.110.100.080.070.050.040.030.010.00 0.12

0.090.080.070.060.050.040.030.030.02 0.100.090.080.070.060.050.040.030.030.02 0.10

dorsalventral ventral

dorsal

Greaves 2008

Von Mises StrainDislocation

0.280.250.210.180.140.110.080.040.00 0.320.280.250.210.180.140.110.080.040.00 0.320.270.230.200.170.130.100.070.030.00 0.300.270.230.200.170.130.100.070.030.00 0.30

dorsalventralventral

dorsal

Greaves 2008

Different Cord Strain Patterns

Greaves Annals BME 2008

Contusion

Theme 3 - Overview

Spinal cord injury represents a

mechanical insult that triggers a

biological response which results in a

wide range of clinical sequelae.

Spinal Injury

FRACTURE DISLOCATION

BURST FRACTURE

FLEXION-DISTRACTION

Do these well-known spinal column injury patterns create different spinal cord injuries?

Injury Models

1970 199019801911 2004

NYU -Gruner

g-cm-Albin

F, IH -Scheff

d, OSU -Noyes

d

Weight drop-Allen

m

h

clip -Tator

Transection

LateralDislocation

-Fiford

Distraction-Maiman

Contusion Paradigm

Figure from McDonald & Belegu. J Neurotrauma 2006

… central cavitation with peripheral rim of spare white matter …

Type of Vertebral Injury

40% Fracture Dislocation

5% Dislocation

Burst Fracture 30%

SCIWORET 10%

SCIWORA 5%

10% Minor Fracture

Sekhon & Fehlings Spine 2001

Experimental Animal Model

Compression/Contusion Shear/Dislocation Distraction

Choo PhD 2006

UBC SCI Test System

Load Cell(22 & 225N)

accelerometer(50 & 500G)

LVDT(0.001mm)

Actuator12mm

Choo PhD 2006

Contusion

5.005 5.01 5.015 5.02-2

-1

0

1

2

3

4

time (s)

dis

pla

cem

ent

(mm

)velo

city

(m

/s)

-2

-1

1

0

4

2

3

forc

e (

N)

Cord surface

Choo PhD 2006

Dislocation

2.995 3 3.005 3.01 3.015-1

-0.5

0

0.5

1

1.5

2

2.5

3

time (s)

dis

pla

cem

ent

(mm

)velo

city

(m

/s)

forc

e (

N)

-10

-5

10

5

30

15

25

20

Choo PhD 2006

Distractiondis

pla

cem

ent

(mm

)velo

city

(m

/s)

0

10

40

20

30

forc

e (

N)

Choo PhD 2006

Hemorrhage

Choo PhD 2006

Anatomy

&

Study 1: Primary Injury

Membrane Integrity

Membrane Integrity

Membrane Damage

Neuronal Cell Bodies Axons

NeuN

Primary Injury• 275-325g Sprague-Dawley rats• Infused 0.375mg 10kD fluorescein dextran into cisterna magna• Incubated for 1 hour + 30 min surgery• Injury ~100cm/s @ C4/5• 5 min sacrifice – primary damage

Mechanism N Severity

Contusion 9 1.1mm

Dislocation 9 2.5mm

Distraction 9 4.1mm

Shams 8 -

Membrane DamageNeuronal Cell Bodies

Lesion RostralInjury

Choo J. Neurosurg. 2007

Membrane DamageAxons

Lesion RostralInjury

Choo J. Neurosurg. 2007

Rostro-Caudal Distribution

Study 2: Early Secondary Injury

Early Secondary Injury• 275-325g Sprague-Dawley rats• Infused 0.375mg 10kD fluorescein dextran into cisterna magna• Incubated for 1 hour + 30 min surgery• Injury @ ~100cm/s• 0.75mg 10kD cascade-blue dextran @ 2hrs

– detect persistent membrane permeability

• 3hrs sacrifice – early secondary

Mechanism N Severity

Contusion 10 1.1mm

Dislocation 10 2.5mm

Distraction 10 4.1mm

Shams 7 -

Dextran Controls 3 -

Membrane Integrity at 3hrs

Pre-injury Dextran Post-injury Dextran Merged Image

Choo Exp. Neurol. 2008

Secondary Axonal Injury

((ββAPP)APP)

Secondary Axonal Injury

Secondary Axonal Injury

Microglial Activation

Activation

Microglial Activation

Act

ivati

on

Choo Exp. Neurol. 2008

Overall Patterns of Tissue Damage

Tissue Damage ≈ Mechanics?

Limitations

• Early time-points for analysis

• Comparable severities?

• Behaviorial differences?

• No therapies tested

Summary

• SCI is a high-speed event that we are characterizing from a biomechanical perspective– Cadaver models– Mathematical models– Small animal models

• Ultimate goal is a clinically relevant sub-classification of SCI

Next Steps…..

• Further characterize primary injury & secondary changes;

• Assess behavioural differences between mechanisms;

• Determine the effectiveness of imaging (MRI) in differentiating between injury mechanisms;

• Evaluate the efficacy of novel therapeutic strategies for spinal cord injury (e.g. neuroprotective, remyelination)

Collaborators

• Anthony Choo• Carolyn Sparrey• Carolyn Greaves• Simon Sjovold• Liz Clarke (AUS)• Amy Saari (PC)• Shannon Reed

(PC)• Tim Bhatnagar• Colin Russell

• Wolfram TetzlaffWolfram Tetzlaff• Peter CriptonPeter Cripton• Marcel DvorakMarcel Dvorak• Brian KwonBrian Kwon• Charles FisherCharles Fisher• Mohamed GadalaMohamed Gadala• Piotr KozlowskiPiotr Kozlowski• Lynne Bilston Lynne Bilston

(AUS)(AUS)

• Qingan ZhuQingan Zhu• Jie LiuJie Liu• Clarrie LamClarrie Lam• Chad LarsonChad Larson• Darrell Darrell

GoertzenGoertzen• Andrew YungAndrew Yung

Acknowledgements

Canada Research Chairs Program

George W. Bagby Research Fund

BC Leading Edge Endowment Fund

Canadian Institutes of Health Research

Rick Hansen Man in Motion Fund

Professor Manohar Panjabi

Yale University

1970-2006

Professor Clive Duncan

Chairman of Orthopaedics at UBC from 1996-2006

Thank you!